Poster Presentation 5th International Symposium on Phaeochromocytoma and Paraganglioma 2017

Anti-tumorigenic and anti-metastatic activity of Aeroplysinin-1, a sponge-derived marine drug on mouse pheochromocytoma cells (#74)

Nicole Bechmann 1 , Hermann Ehrlich 2 , Graeme Eisenhofer 1 , Stefan R. Bornstein 3 , Christian G. Ziegler 3
  1. Institute of Clinical Chemistry and Laboratory Medicine , Technische Universität Dresden, Dresden, Germany
  2. Institute of Experimental Physics, TU Bergakademie Freiberg, Freiberg, Germany
  3. Department of Medicine III, Technische Universität Dresden, Dresden, Germany

Pheochromocytomas and paraganliomas (PPGLs) are neural crest-derived tumors with variable aggressiveness. Over 10% of PPGLs patients have malignant disease at their first surgery with a 5 year survival of >50% (Eisenhofer, et al. 2004). The development of malignancy and the underlying molecular pathways in PPGLs are poorly understood and efficient treatment strategies are missing. Marine sponges provide a natural source of promising anti-tumorigenic and anti-metastatic agents. The present study evaluates the anti-tumorigenic and anti-metastatic potential of Aeroplysinin-1 (García-Vilas, et al. 2015), a secondary metabolite isolated from the marine sponge Aplysina aerophoba, on mouse pheochromocytoma cells (MTT).  

Aeroplysinin-1 decreased cell viability (EC50 = 11.4 µM) and induced apoptosis in a concentration dependent manner. Moreover, treatment with Aerolysinin-1 diminished the number of proliferating cells (2D-culture) and reduced spheroid growth (3D-culture) significantly. The influence of Aeroplysinin-1 on pro-metastatic behavior was analyzed using Boyden Chamber assays. Aeroplysinin-1 decreased the migration ability of the cells significantly (P = 0.01), whereas, the invasion capacity was not affected. MTT cells showed a low adhesion affinity to the extracellular matrix protein fibronectin that is mildly affected by treatment with Aeroplysinin-1. In contrast, Aeroplysinin-1 significantly diminished the high adhesion capacity of the MTT cells to collagen (P < 0.001) and, furthermore, reduced the ability to form spheroids significantly. Ongoing investigations indicate a regulative influence of Aeroplysinin-1 on the expression of the different integrins and cadherins, potentially explaining the inhibitory effects of Aeroplysinin-1 on pro-metastatic behavior.

These in vitro investigations show promise for the application of the sponge-derived marine drug, Aeroplysinin-1 as anti-tumorigenic and anti-metastatic drugs against PPGLs. Furthermore, screening of other sponge-derived secondary metabolites provides an auspicious strategy to identify novel therapeutic strategies for metastatic PPGLs.

  1. Eisenhofer G, Bornstein SR, Brouwers FM, Cheung N-KV, Dahia PL, De Krijger RR, Giordano TJ, Greene LA, Goldstein DS & Lehnert H 2004 Malignant pheochromocytoma: current status and initiatives for future progress. Endocrine-related cancer 11 423-436
  2. García-Vilas JA, Martínez-Poveda B, Quesada AR & Medina MÁ 2015 Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug. Marine drugs 14 1.